Despite the significant interest in therapeutic antibodies for the treatment of airway diseases, no study addressed the challenge, which can arise when such formulations need to be made accessible for nebulization in concentrated (viscous) form. By (1) determining the maximum viscosity, which can still be atomized by vibrating-mesh technology and (2) supplementing the antibody formulation under investigation with at least 1 excipient, which decreases the viscosity under that specific threshold value of the utilized inhaler (and maintains the stability of the formulation), it should be possible to nebulize concentrated antibody formulations. Using sucrose as a viscosity enhancer, the viscosity threshold value amounted to ∼6 mPa*s for the eFlow®rapid device (output rate of <0.1 g/min). When a supplementation of a concentrated model antibody formulation (125 mg/mL) with specific amounts of lysine (≥50 mM) and arginine (≥20 mM) led to the desired drop in viscosity (to <5.5 mPa*s), the previously non-nebulizable formulation (no measurable aerosol output) was made accessible for vibrating-mesh nebulization (output rate of up to ∼0.5 g/min, droplet diameter of <5 μm). The stability of the current antibody formulation was not adversely affected when nebulized in the presence of lysine and arginine. Overall, the presented results will help increase the understanding on how to aerosolize concentrated protein formulations by vibrating-mesh technology.
Keywords: concentrated antibody formulation; droplet size; formulation stability; inhalation; output rate; vibrating-mesh nebulization; viscosity reduction.
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